Denosumab treatment of osteoporotic women arrests cortical bone remodeling events at the reversal-resorption phase but does not affect ongoing bone formation

Q: What was the main focus of the denosumab study in postmenopausal osteoporotic women?

The study focused on cortical remodeling and the transition from erosion to formation after denosumab treatment, using histomorphometric classification of intracortical pores.

Q: How did denosumab affect cortical thickness and pore number compared with placebo?

Cortical thickness was unaffected, and the number of pores per tissue area did not change in the denosumab group versus placebo.

Q: What changes in pore remodeling-stage contributions were observed after denosumab treatment?

Denosumab increased the contribution of eroded pores to total pore area while decreasing the contributions of eroded-formative and formative pores, indicating a largely limited erosion-to-formation transition.

Sep 29, 2026

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Denosumab is an anti-resorptive therapy that lowers fracture risk and increases BMD in postmenopausal osteoporosis. This study examined cortical remodeling and the switch from erosion to formation after denosumab, using histomorphometric classification of intracortical pores. Iliac crest biopsies from the FREEDOM trial (placebo n=43; denosumab n=43; 2–3 years) showed unchanged cortical thickness and pore number, reduced pore diameter, and no reduction in cortical porosity. Denosumab increased eroded pores’ area contribution while decreasing eroded-formative and formative contributions, suggesting inhibited erosion-to-formation transition with refilling of pores already undergoing formation at treatment onset.

LanguageEnglish

CategoryResearch & Report

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Pages11

Reading Time28 min

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JBMR Plus, 2026, 10, ziaf181 [https://doi.org/10.1093/jbmrpl/ziaf181](https://doi.org/10.1093/jbmrpl/ziaf181) Advance access publication: November 22, 2025 Research Article Denosumab treatment of osteoporotic women arrests cortical bone remodeling events at the reversal-resorption phase but does not affect ongoing bone formation Xenia Goldberg Dahl1 , * , Jean-Paul Roux2 , Jean-Marie Delaisse1 , Shuang Huang3 , Pascale Chavassieux2 , Christina M. Andreasen1 ,4 , Thomas L. Andersen1 ,4 ,5 1 Molecular Bone Histology Team, Research Unit of Pathology, Department of Clinical Research, University of Southern Denmark, 5230 Odense M, Denmark 2 Univ Lyon, INSERM, UMR 1033, UFR de Médecine Lyon-Est, F-69008 Lyon, France 3 Center for Design and Analysis, Amgen Inc., Thousand Oaks, CA 91320, United States 4 Department of Pathology, Odense University Hospital, 5000 Odense, Denmark 5 Department of Forensic Medicine, Aarhus University, 8200 Aarhus N, Denmark *Corresponding author: Xenia Goldberg Dahl, Molecular Bone Histology Team, Research Unit of Pathology, Department of Clinical Research, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark ([xborggaard@health.sdu.dk](xborggaard@health.sdu.dk)) . Abstract Denosumab is an anti-resorptive therapy that effectively reduces fracture risk and increases BMD in women with postmenopausal osteoporosis. In this study, we focused on the less well-investigated cortical remodeling process and its transition from erosion to formation after denosumab treatment, using a histomorphometric classiﬁcation of intracortical pores. Cortical bone is more prominent in non-vertebral bones, where denosumab is less effective in fracture reduction. In iliac crest biopsies from the FREEDOM-study, where postmenopausal osteoporotic women were treated with placebo (n=43) or denosumab (n=43) for 2-3 yr, the cortical microstructure and remodeling stage and type of intracortical pores were analyzed. Cortical thickness was unaffected in the denosumab group vs placebo (P= .9) . Mean pore diameter was signiﬁcantly decreased in the denosumab group vs placebo ( P < .002) with no change in the number of pores per tissue area ( P = .83) . However, the cortical porosity was not decreased in the denosumab vs placebo group ( P < .077) . When stratifying the pores according to their remodeling stage, the eroded pores had an increased contribution to the total pore area in the denosumab vs placebo group ( P = .001) . Eroded-formative and formative pores had a decreased contribution to the total pore area ( P < .001) . The contribution of quiescent pores was unchanged. The increased contribution of eroded pores and the concomitant reduced contribution of eroded-formative and formative pores indicate that the transition from erosion to formation is largely limited, while pores with ongoing bone formation at the time of initiation of denosumab treatment are reﬁlled. Keywords: bone modeling and remodeling, osteoporosis, antiresorptives, osteoblasts, osteoclasts Lay Summary Denosumab improves bone density and reduces the risk of fractures in women with postmenopausal osteoporosis. This study investigateshow denosumab affects tiny holes (pores) in cortical bone and how bone breaks down and rebuilds. We found that denosumab made the pores smaller, while they remained the same in terms of number. Denosumab also caused more pores to stay in a broken-down state and fewer to move into the rebuilding phase, suggesting denosumab may stop bone breakdown without promoting repair. Introduction Osteoporosis is a skeletal disease characterized by low bone mass, leading to increased bone fragility and fracture risk.1 Despite intensive research and several therapeutic agents being available for treatment of osteoporosis, long-term treatment with continued effects and without increasing the risk of adverse effects remains a challenge.2 ,3 Furthermore, the available treatments differ in their ability to red

FAQs

What was the main focus of the denosumab study in postmenopausal osteoporotic women?

The study focused on cortical remodeling and the transition from erosion to formation after denosumab treatment, using histomorphometric classification of intracortical pores.

How did denosumab affect cortical thickness and pore number compared with placebo?

Cortical thickness was unaffected, and the number of pores per tissue area did not change in the denosumab group versus placebo.

What changes in pore remodeling-stage contributions were observed after denosumab treatment?

Denosumab increased the contribution of eroded pores to total pore area while decreasing the contributions of eroded-formative and formative pores, indicating a largely limited erosion-to-formation transition.

Sep 29, 2026

Upload by Sarah